Interrelationship between Fatty Acid Oxidation and Gluconeogenesis from Pyruvate

1 Both glucagon (93 nM) and N6, O2′-dibutyryl cyclic adenosine 3′:5′-phosphate (Bu2Ado-3′:5′-P) (10 μM) stimulated gluconeogenesis from pyruvate to the extent of 35% in the perfused liver from fasted rats. Under these conditions, all of the pyruvate disappearance could be accounted for in lactate and glucose. When livers were perfused with pyruvate only, a portion of the pyruvate metabolized was unaccounted for, and presumably oxidized. 2 Bu2Ado-3′:5′-P, even in the presence of glycodiazine, stimulated gluconeogenesis from pyruvate and lowered the ratio of C3 uptake to glucose ratio, suggesting a “sparing effect” on pyruvate oxidation. 3 (+)-Decanoylcarnitine (0.5 mM) blocked a significant portion of the stimulation of gluconeogenesis by glucagon (93 nM). Other parameters of pyruvate metabolism were unaltered by the carnitine ester in the presence of glucagon. In contrast, Bu2Ado-3′:5′-P (10 μM) in the presence of (+)-decanoylcarnitine significantly increased glucose formation in comparison to livers perfused only with the carnitine derivative. 4 Pentenoic acid (1.0 mM) resulted in a 50% inhibition of gluconeogenesis, a lowered pyruvate disappearance and an increase of pyruvate unaccounted for and presumably oxidized. Livers perfused with 4-pentenoic acid in addition to glucagon exhibited a marked suppression of gluconeogenesis, a decreased conversion of pyruvate to lactate and a lowered pyruvate disappearance rate. 5 Livers perfused with Bu2Ado-3′:5′-P (10 μM) in addition to 4-pentenoic acid, when compared to livers perfused with 4-pentenoic acid, exhibited a significantly increased rate of gluconeogenesis. Bu2-Ado-3′:5′-P exerted a “sparing effect” on pyruvate carbon even in the presence of 4-pentenoic acid.